Physiochemical properties of phenobarbital solid dispersion with phosphatidylcholine.
We prepared a phenobarbital (PB) solid dispersion (SD) with phosphatidylcholine (PC). PB was present in an amorphous state in SD if its mole fraction was under 0.75. An infrared (IR) spectra study suggested a hydrogen bond between NH in PB and phosphate in PC, with a ratio of about 1:1. When the mole fraction of PB was less than 0.50, differential scanning calorimetry (DSC) curves showed endothermic peaks at 57, 90 and 145 degrees C, and an exothermic peak at 60 degrees C. The IR spectrum and X-ray diffraction pattern changed after holding at 70 degrees C, so at this point it is considered that the metastable state of SD changed into a stable state, and extra energy was released. When the mole fraction of PB was high, PB also arranged near hydrophobic group because an endothermic peak was observed at 46-52 degrees C, which was lower than fully hydrated PC. PB is similar to indomethacin (IM) in molecular shape and to phenytoin (PHT) in chemical structure. Its DSC curve and IR spectra are similar to PHT, and the limit ratio of its amorphous state is the same as IM. It is considered that the chemical structure is an important factor in its interaction to PC, and also, the molecular shape is important to arrange into PC lattice.
Fujii
M
M
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Harada
K
K
Matsumoto
M
M
D002152:Calorimetry, Differential Scanning; D005583:Fourier Analysis; D008968:Molecular Conformation; D010634:Phenobarbital / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
D010713:Phosphatidylcholines; D010634:Phenobarbital